tbuckley/cabot-search huggingface dataset:
Functional hepatocyte heterogeneity in glutamate, aspartate and α-ketoglutarate uptake: A histoautoradiographical study
Authors: Barbara Stoll, Sabine McNelly, Hans-Peter Buscher, Dieter Häussinger
Journal: Hepatology (1991)

[ 3 H]glutamate, [ 3 H]α-ketoglutarate or [ 3 H]aspartate was injected in physiological concentrations into antegrade (from portal to hepatic vein) or retrograde (from hepatic to portal vein) perfused rat liver, and the tissue distribution of radioactivity was studied by histoautoradiography. Independent of the direction of perfusion, radioactivity was accumulated in a small perivenous liver parenchymal cell population, which surrounded the terminal hepatic venules as a layer of about two to five cells thick. In contrast, accumulation of radioactivity in periportal hepatocytes was low and sometimes not detectable. This distribution pattern roughly resembled that described for the immunohistochemical distribution of glutamine synthetase in liver. The present histoautoradiographic findings demonstrate a predominant uptake of vascular glutamate, aspartate and ketoglutarate into a small perivenous cell population. They confirm previous label incorporation studies in the metabolically intact liver, demonstrating an almost exclusive uptake of vascular glutamate and α-ketoglutarate into perivenous glutamine synthetase containing hepatocytes. In addition, evidence is presented suggesting that perivenous uptake of α-ketoglutarate may be one determinant for hepatic glutamine synthesis, at least under the experimental conditions used here. (Hepatology 1991;13:247-253).
Eosinophilia-Myalgia Syndrome
Authors: Leslie A. Swygert
Journal: JAMA (1990)

Eosinophilia-myalgia syndrome, a newly recognized disorder that occurred in epidemic proportions during 1989, is associated with ingestion of manufactured tryptophan. A case is defined by debilitating myalgias and absolute eosinophilia greater than or equal to 1.0 × 10<sup>9</sup>cells/L. As of July 10,1990, a total of 1531 cases had been reported nationwide, including 27 deaths. The highest rates of reported illness are concentrated in the western states, 68% are non-Hispanic white women aged 35 years and older, and data on associated clinical findings suggest a multisystemic disorder. The most frequent features include arthralgia (73%), rash (60%), cough or dyspnea (59%), peripheral edema (59%), elevated aldolase level (46%), and elevations in the results of liver function tests (43%). Neuropathy or neuritis, resulting in paralysis and death in some patients, was seen in 27%, and chest roentgenogram abnormalities were noted in 21% of those tested. Ninety-one percent reported onset of symptoms during or after May 1989, and 97% reported having taken tryptophan before the onset of symptoms. Since the recall of over-the-counter preparations of tryptophan in November 1989, the number of new cases of this potentially fatal disorder has fallen dramatically. (<i>JAMA</i>. 1990;264:1698-1703)
Zolbetuximab + CAPOX in 1L claudin-18.2+ (CLDN18.2+)/HER2− locally advanced (LA) or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: Primary phase 3 results from GLOW.
Authors: Rui-hua Xu, Kohei Shitara, Jaffer A. Ajani, Yung-Jue Bang, Peter C. Enzinger, David H. Ilson, Florian Lordick, Eric Van Cutsem, Javier Gallego Plazas, Jing Huang, Lin Shen, Sang Cheul Oh, Patrapim Sunpaweravong, Hwoei Fen Soo Hoo, Haci M. Turk, Jung Wook Park, Diarmuid Martin Moran, Pranob P. Bhattacharya, Ahsan Arozullah, Manish A. Shah
Journal: Journal of Clinical Oncology (2023)

405736 Background: There is an unmet need for novel targeted therapies that improve outcomes for pts with HER2− LA unresectable or mG/GEJ adenocarcinoma. CLDN18.2 is expressed in normal gastric mucosa cells and retained in most G/GEJ adenocarcinomas. In the phase 3 SPOTLIGHT study, zolbetuximab, a CLDN18.2-targeted chimeric monoclonal antibody, significantly prolonged PFS and OS in pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma when combined with mFOLFOX6. GLOW (NCT03653507) is a phase 3 global, double-blind study comparing zolbetuximab or PBO with capecitabine and oxaliplatin (CAPOX) as 1L treatment for this pt population. Methods: Pts with CLDN18.2+ (moderate-to-strong membranous CLDN18 staining in ≥75% tumor cells by IHC)/HER2− LA unresectable or mG/GEJ adenocarcinoma were randomized 1:1 to zolbetuximab IV 800 mg/m 2 (cycle 1, day [D] 1) followed by 600 mg/m 2 (D1 in subsequent cycles) + CAPOX (oral capecitabine 1000 mg/m 2 BID on D1−14 of each cycle; oxaliplatin IV 130 mg/m 2 on D1 of each cycle) for eight 21-day cycles vs PBO + CAPOX; pts continued for &gt;8 cycles with zolbetuximab or PBO, plus capecitabine (investigator decision), until PD or a discontinuation criterium was met. The primary endpoint (EP) was PFS per RECIST v1.1 by IRC. OS was a key secondary EP; other secondary EPs included ORR and safety. Differences between treatment arms in PFS and OS were tested by stratified log-rank tests; OS was tested if PFS was significant. Results: 507 pts were randomized 1:1 to zolbetuximab + CAPOX (N = 254) or PBO + CAPOX (N = 253). Both PFS (median 8.21 vs 6.80 mo, HR 0.687, P=0.0007) and OS (median 14.39 vs 12.16 mo, HR 0.771, P=0.0118) were significantly prolonged with zolbetuximab + CAPOX (Table); in pts with measurable disease, ORR (95% CI) was 53.8% (46.58−60.99) vs 48.8% (41.76−55.84) in zolbetuximab vs PBO arm. The most common TEAEs with zolbetuximab + CAPOX were nausea (68.5% vs 50.2% in zolbetuximab vs PBO arm), vomiting (66.1% vs 30.9%), and decreased appetite (41.3% vs 33.7%); serious TEAEs (47.2% vs 49.8%), grade ≥3 TEAEs (72.8% vs 69.9%), and drug-related TEAEs leading to death (2.4% vs 2.8%) were similar in both arms. Conclusions: Targeting CLDN18.2 with zolbetuximab combined with CAPOX significantly prolonged PFS and OS in 1L pts with CLDN18.2+/HER2− LA unresectable or mG/GEJ adenocarcinoma. These results align with those observed in SPOTLIGHT and establish zolbetuximab + chemotherapy as a potential new standard-of-care option for these pts. Clinical trial information: NCT03653507 . [Table: see text]
The Case-Control Study
Authors: Gregory F. Hayden
Journal: JAMA (1982)

The retrospective case-control study is an important research strategy commonly encountered in the medical literature. A thoughtfully designed, carefully executed case-control study can be an invaluable source of clinical information, and physicians must often base important decisions about patient counseling and management on their interpretation of such studies. Unfortunately, the retrospective direction of case-control studies—looking "backwards" from an outcome event to an antecedent exposure—is accompanied by numerous methodological hazards. Careful attention must be paid to selection of appropriate study groups; definition and detection of the outcome event; definition and ascertainment of the exposure; assurance that the compared groups were equally susceptible to the outcome event at baseline; and careful statistical analysis. If systematic bias enters the research at any of these points, erroneous conclusions can result. Greater familiarity with the case-control method should enable clinicians to be more critically insightful when interpreting the results of published studies using this design format. (<i>JAMA</i>1982;247:326-331)
Physicians and the Organizational Evolution of Medicine
Authors: R. Clay Burchell
Journal: JAMA (1988)

Within medicine there is growing uneasiness and debate about changes in medical care delivery. Much of this concern centers on the evolution of organizations and the role of physicians. The emergence of multi-institutional organizations, the rise of investor-owned health care corporations, and the expansion of group medical practice illustrate the increasing organizational influence in medicine. Added to these trends are new financial incentives confronting both physicians and organizations so that the environment increasingly favors conflict. This article reviews the primary strategies for resolving physician-organization conflicts, including cooperation between physicians and organizations, having physician representatives in governance and management, restructuring incentives, and restructuring organizations. Although these strategies have various merits, we suggest that every physician has a personal responsibility to become more involved in organization and management issues. Physicians can play an important role in guiding the evolution of medicine. (<i>JAMA</i>1988;260:826-831)
Boxing-Related Injuries in the US Army, 1980 Through 1985
Authors: Robert W. Enzenauer
Journal: JAMA (1989)

Boxing-related injuries, serious enough to involve hospitalization in US Army hospitals, were studied from 1980 through 1985. On average, there were 67 hospitalizations annually, with the injured spending an average of 5.1 days in bed and 8.9 days disabled, unfit for duty. There was one death from serious head injury and one instance of unilateral blindness from ocular trauma requiring enucleation. Head injuries accounted for 68% of all the injuries and were more common in the younger and presumably less experienced boxers. The advisability of continued promotion of boxing in the military needs to be addressed. (<i>JAMA</i>1989;261:1463-1466)
A Patient With Diabetes and Spontaneous Blistering of the Right Lower Extremity
Authors: Madeline DeWane, Daniela Kroshinsky
Journal: JAMA (2023)

A 42-year-old patient with hypertension and type 2 diabetes had hyperpigmented macules on the anterior legs below the knees and tense, painless bullae on the right leg, with no surrounding erythema or edema; findings on the remainder of the skin and mucocutaneous examination were unremarkable. What is the diagnosis and what would you do next?
Analysis of Psychiatric Symptoms and Suicide Risk Among Younger Adults in China by Gender Identity and Sexual Orientation
Authors: Shufang Sun, Shicun Xu, Arryn Guy, John Guigayoma, Yanwen Zhang, Yuanyuan Wang, Don Operario, Runsen Chen
Journal: JAMA Network Open (2023)

Younger adults in China who are transgender and gender nonconforming (TGNC) and lesbian, gay, and bisexual (LGB) experience high levels of minority stress (eg, stigma and bullying) and adverse mental health symptoms. However, there is a lack of research documenting mental health disparities compared with their cisgender and heterosexual peers. Studies that disaggregate TGNC and LGB individuals and are conducted in nonmetropolitan regions are also needed. To examine whether younger adult students' psychiatric symptoms and suicide risk vary by sexual orientation and gender identity and identify risk factors within LGB younger adults and TGNC younger adults. This cross-sectional study surveyed students at 63 universities in Jilin Province, China, between October 24 and November 18, 2021. Analyses were completed May 6, 2022. Gender identity (TGNC vs cisgender) and sexual orientation (LGB vs heterosexual). Psychiatric outcomes included depression, anxiety, traumatic stress, and nonsuicidal self-injury (NSSI), which were measured by the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Trauma Screening Questionnaire, and self-reported NSSI behaviors. The Suicide Behaviors Questionnaire-Revised was used to assess suicide risk. The analytic sample included 89 342 younger adults (mean [SD] age, 19.60 [1.75] years), including 51 438 assigned female at birth and 37 904 assigned male at birth. The sample included 2352 individuals who were TGNC, 6501 who were cisgender LGB, and 80 489 who were cisgender heterosexual. Compared with their cisgender heterosexual peers, TGNC and LGB younger adults were more likely to experience increased psychiatric symptoms across categories and suicide risk, as well as more severe forms of symptoms. In particular, overall suicide risk was 43.03% among TGNC individuals, 36.21% among LGB individuals, and 11.70% among cisgender heterosexual younger adults. Controlling for demographic variables and compared with cisgender heterosexual peers, TGNC young adults had higher odds of suicide risk (adjusted odds ratio, 5.38; 95% CI, 4.94-5.86; P < .001) and of past-year NSSI (adjusted odds ratio, 6.55; 95% CI, 5.87-7.30; P < .001). Separate within-group analyses for LGB and TGNC younger adults highlighted the vulnerability of bisexual women and gender nonbinary groups, as well as the relevance of minority stress-related risk factors, including peer bullying and assault and loneliness. This study noted disparities of mental health issues among LGB, transgender, or queer or questioning younger adults in China and suggests a high urgency to address psychological health and prevent suicide in this population. Targeted public health initiatives may be needed to reduce stigma and discrimination, train competent health care professionals, and create affirmative mental health policies and systems of care.
Air Pollution and Mortality at the Intersection of Race and Social Class
Authors: Kevin P. Josey, Scott W. Delaney, Xiao Wu, Rachel C. Nethery, Priyanka DeSouza, Danielle Braun, Francesca Dominici
Journal: New England Journal of Medicine (2023)

Black Americans are exposed to higher annual levels of air pollution containing fine particulate matter (particles with an aerodynamic diameter of ≤2.5 μm [PM
Food Insecurity and Cognitive Trajectories in Community-Dwelling Medicare Beneficiaries 65 Years and Older
Authors: Boeun Kim, Laura J. Samuel, Roland J. Thorpe, Deidra C. Crews, Sarah L. Szanton
Journal: JAMA Network Open (2023)

Food insecurity has a known association with prevalent impaired cognition. However, it is unknown whether food insecurity has a longitudinal association with cognitive decline among older adults.To determine whether food insecurity is associated with a faster decline in cognitive function among community-dwelling older adults.This retrospective cohort study used data from a nationally representative sample of Medicare beneficiaries 65 years and older recruited for the National Health and Aging Trends Study (NHATS). Community-dwelling NHATS participants were followed up for a maximum of 7 years (mean [SD] follow-up duration, 5.4 [1.1] years). Data were collected from January 1, 2012, to December 31, 2020, and analyzed from December 23, 2021, to December 6, 2022.Self-reported food insecurity assessed from 2012 to 2019.Primary outcomes were immediate memory, delayed memory, and executive function collected from 2013 to 2020. Immediate and delayed recall were assessed by a 10-item word-list memory task (range, 0-10, with higher scores indicating more words recalled). Executive function was measured by the clock drawing test (range, 0-5, with higher scores indicating more accurate depiction of a clock). Each year's cognitive functions were linked to the prior year's food insecurity data. Linear mixed-effects models with random slopes and intercepts were used to examine the association between food insecurity and cognitive decline. Analytic weights in each year were applied to represent community-dwelling Medicare beneficiaries 65 years and older in 2011.Of 3037 participants, a weighted 57.8% (raw count, 1345) were younger than 75 years, 56.2% (raw count, 1777) were women, and most (84.9% [raw count, 2268]) were White. Over 7 years, 417 (weighted proportion, 12.1%) experienced food insecurity at least once. Food insecurity was associated with a faster decline in executive function in a fully adjusted model: the mean difference of annual change in executive function score between people exposed to and not exposed to food insecurity was -0.04 (95% CI, -0.09 to -0.003) points. However, food insecurity was not associated with changes in immediate and delayed memory (0.01 [95% CI, -0.05 to 0.08] and -0.01 [95% CI, -0.08 to 0.06], respectively).Among community-dwelling older adults, food insecurity was prevalent and associated with a decline in executive function. Interventions and policies aiming to increase healthy food access or reduce food insecurity should be assessed for their impact on older adults' cognitive outcome.
Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?
Authors: Isabella Annesi‐Maesano, Lorenzo Cecchi, Benedetta Biagioni, Kian Fan Chung, Bernard Clot, Martine Collaud Coen, Gennaro D'Amato, Athanasios Damialis, Javier Dominguez‐Ortega, Carmen Galàn, Stefanie Gilles, Stephen Holgate, Mohamed Jeebhay, Stelios Kazadzis, Nikolaos G. Papadopoulos, Santiago Quirce, Joaquin Sastre, Fiona Tummon, Claudia Traidl‐Hoffmann, Jolanta Walusiak‐Skorupa, Pablo Alonso‐Coello, Carlos Canelo‐Aybar, Yahveth Cantero‐Fortiz, David Rigau, Josefina Salazar, Francisca Verdugo‐Paiva, Marek Jutel, Cezmi A. Akdis, Ioana Agache
Journal: Allergy (2023)

Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation, but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations, and an increase in grass pollen concentration in the previous 2-day overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7-day overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age, an exposure to grass pollen lagged up to 3 days may lower lung function. Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces, and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change.
Programmed-response cross-linked nanocarrier for multidrug-resistant ovarian cancer treatment
Authors: Haijing Qu, Jinfan Yang, Shuaijun Li, Ji Xu, Xin Zhou, Xiangdong Xue, Dalin Zhang, Hongxu Du, Yingbin Shen, Mythili Ramachandran, Hongbo Zheng, Yi Wu, Yifan Ding, Hao Wu, Xiaobin Ma, Tzu-Yin Lin, Yuanpei Li
Journal: Journal of Controlled Release (2023)
YAP and β-catenin cooperate to drive <i>H. pylori</i> -induced gastric tumorigenesis
Authors: Nianshuang Li, Xinbo Xu, Yuan Zhan, Xiao Fei, Yaobin Ouyang, Pan Zheng, Yanan Zhou, Cong He, Chuan Xie, Yi Hu, Junbo Hong, Nonghua Lu, Zhongming Ge, Yin Zhu
Journal: Gut Microbes (2023)

H. pylori infection is the strongest known risk factor for gastric carcinoma. The activation of the yes-associated protein 1 (YAP) and β-catenin pathways has been associated with multiple tumor types. In this study, we investigated the crosstalk between the YAP and β-catenin pathways in H. pylori-associated gastric tumorigenesis. Immunohistochemical analysis of YAP and β-catenin expression was performed in human gastric cancer tissues. The small molecules Super-TDU and KYA1797K, pharmacological inhibitors of YAP and β-catenin, respectively, were used to investigate the role of these signaling pathways in H. pylori-induced gastric carcinogenesis in murine models of infection. The common downstream targets of YAP and β-catenin signaling were evaluated by RNA sequencing (RNA-seq). Western blot, immunofluorescence, luciferase, RT-PCR, immunoprecipitation, cell counting kit-8 (CCK8), EdU and spheroid assays were used. H. pylori infection promoted YAP and β-catenin nuclear accumulation and transcriptional activity in gastric epithelial cells and transgenic insulin–gastrin (INS-GAS) mice, whereas silencing of both YAP and β-catenin synergistically inhibited H. pylori-induced cell proliferation and expansion. In addition, YAP was found to directly interact with β-catenin and knockdown of YAP suppressed H. pylori-induced nuclear translocation of β-catenin. Moreover, downstream genes caudal-type homeobox 2 (CDX2), leucine-rich repeat containing G protein-coupled receptor 5 (LGR5) and RuvB like AAA ATPase 1 (RUVBL1) were shared by both YAP and β-catenin signaling. Furthermore, treatment with the YAP inhibitor Super-TDU or β-catenin inhibitor KYA1797A significantly alleviated gastric inflammation and epithelial DNA damage in H. pylori-infected mice. Finally, the elevation of gastric YAP was positively correlated with β-catenin expression in human gastric cancer tissues. These findings indicate that YAP and β-catenin synergistically promote H. pylori-induced gastric carcinogenesis via their physical interaction and reveal that CDX2, LGR5 and RUVBL1 are the downstream genes shared by both the YAP and β-catenin signaling pathways, and potentially contribute to H. pylori pathogenesis.
Effect of tenofovir-based HIV pre-exposure prophylaxis against HBV infection in men who have sex with men
Authors: Daisuke Mizushima, Misao Takano, Takahiro Aoki, Naokatsu Ando, Haruka Uemura, Yasuaki Yanagawa, Koji Watanabe, Hiroyuki Gatanaga, Yoshimi Kikuchi, Shinichi Oka
Journal: Hepatology (2023)

Background and Aims: Men who have sex with men (MSM) are vulnerable to contracting HBV as a sexually transmitted infection. We evaluated the incidence of HBV infection (HBI) and the prophylactic effect of tenofovir-based pre-exposure prophylaxis (PrEP) on HBI in an MSM cohort. Methods and Results: MSM who were older than 16 years were enrolled from January 2018 and followed up until June 2021 and tested for HIV, bacterial sexually transmitted infections, and HBsAg/ HBsAb and HBcAb every 3 months based on inclusion criteria, including HBsAg, HBcAb, HBsAb, and HIV negativity at enrollment. HBI was defined as seroconversion of HBsAg or HBcAb status. The log-rank test was used to evaluate the prophylactic effect of PrEP against HBI. As a substudy, individuals excluded from the main study due to HBs Ab positivity were evaluated for HBI incidence. Among 1577 MSM, 786 participants (546 PrEP nonusers, 131 daily PrEP users, and 109 event-driven PrEP users) met the criteria and were included. The annual incidence of HBV among PrEP nonusers (3.8%, 21 infections, with 559.5 person-years) was significantly higher ( p = 0.018, log-rank test) than that among daily PrEP users [0.77%, 1 infection (admitted nonadherence), with 129.3 person-years] and event-driven PrEP users (no infection with 93.8 person-years). Although the incidence of HBI and HIV infection decreased with PrEP use, the incidence of other sexually transmitted infections was higher in both daily and event-driven PrEP users. The annual incidence of HBV among HBsAb-positive and HBcAb-negative PrEP nonusers was 1.8% (3 infections, with 167.5 person-years). Conclusions: Tenofovir-based PrEP prevented HBI among MSM in a real-world setting.
Evaluation of Training to Increase Knowledge of the Addendum Guidelines for the Prevention of Peanut Allergy in the US
Authors: Waheeda Samady, Lucy A. Bilaver, Jialing Jiang, Anahita Iyer, Joy Laurienzo Panza, Alkis Togias, Ruchi S. Gupta
Journal: JAMA Network Open (2023)

This survey study examines changes in pediatric clinicians’ knowledge of eczema identification and the 2017 Addendum Guidelines for the Prevention of Peanut Allergy after an educational intervention.